Diethyl Ether → HCID 20382379, compound

HRID 1448350Notes

Reaction equation

HRID 1448350 reaction equation
[Li].[O:2]([CH2:5][CH3:6])CC.IC.[CH3:9][CH:10]([N:12]1[CH2:17][CH2:16][C:15]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)(C(O)=O)[CH2:14][CH2:13]1)[CH3:11]>O>[CH3:11][CH:10]([N:12]1[CH2:17][CH2:16][C:15]([C:5](=[O:2])[CH3:6])([NH:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:14][CH2:13]1)[CH3:9]

Participants

6

Reactant 4

HCID 3283Diethyl Ether3×HCID 6328Methyl iodideHCID 3028194Lithium2×HCID 20382368HCID 20382368, compound

Product 1

HCID 20382379HCID 20382379, compoundYield 33.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

To a stirred mixture of 13.8 parts of lithium and 140 parts of 1,1'-oxybisethane is added dropwise a mixture of 156 parts of iodomethane and 140 parts of 1,1'-oxybisethane while nitrogen gas is introduced. After the addition is complete, there are added 420 parts of 1,1'-oxybisethane and stirring is continued at reflux temperature till all lithium has reacted (about 15 minutes). Then there are added portionwise 26.25 parts of 1-(1-methylethyl)-4-(phenylamino)-4-piperidinecarboxylic acid (exothermic reaction: reflux temperature is maintained) while nitrogen gas is still introduced. Upon completion, stirring at reflux is continued for 1.50 hours. After the nitrogen gas introduction is stopped, the reaction mixture is cooled to 5° C. and decomposed by pouring onto 600 parts of water. The organic phase is separated, washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume), saturated with ammonia, as eluent. The pure fractions are collected and the eluent is evaporated. The residue is crystallized from petroleumether at 0° C. The product is filtered off and dried, yielding 8.7 parts (33.5%) of 1-[1-(1-methylethyl)-4-(phenylamino)-4-piperidinyl]ethanone; mp. 107.1° C.

Workup

  1. additionis added dropwise
  2. additionis introduced
  3. additionAfter the addition
  4. customhas reacted (about 15 minutes)
  5. additionis still introduced
  6. stirringUpon completion, stirring
  7. temperatureat reflux
  8. customThe organic phase is separated
  9. washwashed with water
  10. customdried
  11. filtrationfiltered
  12. customevaporated
  13. customThe residue is purified by column-chromatography over silica gel using
  14. additiona mixture of trichloromethane and methanol (95:5 by volume)
  15. customThe pure fractions are collected
  16. customthe eluent is evaporated
  17. customThe residue is crystallized from petroleumether at 0° C
  18. filtrationThe product is filtered off
  19. customdried

Sources & evidence

ORD record
ord-2216cf2234bd4321b202240e4721096d
Source dataset
uspto-grants-1979_12
Patent number
US04179569

Reaction notes

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